Mitochondrial Unfolded Protein Response and Its Roles in Stem Cells

Shen, Guo‐Ping; Liu, Wei; Xu, Lvwan; Wang, Lin-Lin

doi:10.1089/scd.2019.0278

Cited by 15 publications

(6 citation statements)

References 121 publications

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“…Researchers have made significant efforts to find mechanisms that can keep stem cells young, such as the mitochondrial unfolded protein response ( Shen et al, 2020 ). However, it is also important to identify a mechanism that can induce stem cell senescence.…”

Section: Discussionmentioning

confidence: 99%

A Novel Age-Related Circular RNA Circ-ATXN2 Inhibits Proliferation, Promotes Cell Death and Adipogenesis in Rat Adipose Tissue-Derived Stromal Cells

Song

Xing

et al. 2021

Front. Genet.

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Adipose tissue-derived stromal cells are promising candidates investigating the stem cell-related treatment. However, their proportion and utility in the human body decline with time, rendering stem cells incompetent to complete repair processes in vivo. The involvement of circRNAs in the aging process is poorly understood. Rat subcutaneous adipose tissue from 10-week-old and 27-month-old rats were used for hematoxylin and eosin (H and E) staining, TUNEL staining, and circRNA sequencing. Rat adipose tissue-derived stromal cells were cultured and overexpressed with circ-ATXN2. Proliferation was examined using xCELLigence real-time cell analysis, EdU staining, and cell cycle assay. Apoptosis was induced by CoCl2 and examined using flow cytometry. RT-PCR assay and Oil Red O staining were used to measure adipogenesis at 48 h and 14 days, respectively. H and E staining showed that the diameter of adipocytes increased; however, the number of cells decreased in old rats. TUNEL staining showed that the proportion of apoptotic cells was increased in old rats. A total of 4,860 and 4,952 circRNAs was detected in young and old rats, respectively. Among them, 67 circRNAs exhibited divergent expression between the two groups (fold change ≥2, p ≤ 0.05), of which 33 were upregulated (49.3%) and 34 were downregulated (50.7%). The proliferation of circ-ATXN2-overexpressing cells decreased significantly in vitro, which was further validated by xCELLigence real-time cell analysis, EdU staining, and cell cycle assay. Overexpression of circ-ATXN2 significantly increased the total apoptotic rate from 5.78 ± 0.46% to 11.97 ± 1.61%, early apoptotic rate from 1.76 ± 0.22% to 5.50 ± 0.66%, and late apoptosis rate from 4.02 ± 0.25% to 6.47 ± 1.06% in adipose tissue-derived stromal cells. Furthermore, in circ-ATXN2-overexpressing cells, RT-PCR assay revealed that the expression levels of adipose differentiation-related genes PPARγ and CEBP/α were increased and the Oil Red O staining assay showed more lipid droplets. Our study revealed the expression profile of circRNAs in the adipose tissue of old rats. We found a novel age-related circular RNA—circ-ATXN2—that inhibits proliferation and promotes cell death and adipogenesis in rat adipose tissue-derived stromal cells.

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Section: Discussionmentioning

confidence: 99%

A Novel Age-Related Circular RNA Circ-ATXN2 Inhibits Proliferation, Promotes Cell Death and Adipogenesis in Rat Adipose Tissue-Derived Stromal Cells

Song

Xing

et al. 2021

Front. Genet.

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“…Mitochondrial chaperones are capable of helping misfolded proteins return to their normal conformation, and aid newly synthesized proteins in folding accurately, while proteases are capable of degrading useless proteins (14)(15)(16). Recent research has revealed that UPRs mt are involved in maintaining stem cell homeostasis, promoting tissue regeneration, and prolonging lifespan (17). Losing UPR mt components has a profound effect on cell proliferation, by activating UPR mt components, hematopoietic stem cells (HSCs) can transit from quiescence to proliferation (17).…”

Section: Original Articlementioning

confidence: 99%

“…Recent research has revealed that UPRs mt are involved in maintaining stem cell homeostasis, promoting tissue regeneration, and prolonging lifespan ( 17 ). Losing UPR mt components has a profound effect on cell proliferation, by activating UPR mt components, hematopoietic stem cells (HSCs) can transit from quiescence to proliferation ( 17 ). Additionally, UPR mt plays a role in dedifferentiating cells and obtaining stem cell-like properties during tissue remodeling ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Knowledge mapping of research on the mitochondrial unfolded protein response: a bibliometric and visual analysis

Zhu¹,

Sun²,

Fan³

et al. 2023

Ann Transl Med

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Background The mitochondrial unfolded protein response (UPR mt ) is a mitochondria stress response, which exerts a crucial role in maintaining mitochondrial proteostasis during stress. However, there is no bibliometric analyses systematically studied this field which could comprehensively review research trends, evaluate publication performances and provide future perspectives. Methods Articles investigating UPR mt published between 1994 and 2021 were downloaded from the Core Collection of the Web of Science (WOS). CiteSpace and VOSviewer bibliometric software were applied for bibliometric and visual analyses. Results A total of 2,073 papers researching UPR mt were retrieved. According to the published number of papers, the field of UPR mt research has gone through its infancy (after 2000) and rapid growth (after 2021) phases. The United States and China contributed the most to UPR mt research. Regarding the distribution of institutions, Harvard University was the most influential institution. The most prolific authors are Johan Auwerx and CM Haynes. PLoS One is the most extensive journal in the field of UPR mt research, while the Cell Death and Differentiation journal had the greatest impact among the most-authored journals. Moreover, biochemistry/molecular biology, and cell biology are the largest subject areas. UPR mt research is mainly categorized as UPR mt , transcription, endoplasmic reticulum (ER) stress, lipotoxicity, mitophagy, inflammation, skeletal muscle, hypoxia, apoptosis, mitochondrial dysfunction, neurodegeneration, mitochondrial permeability transition, and integrated stress response. Conclusions At present, research on UPR mt is booming. Further strengthening the cooperation and exchanges between countries, institutions, and authors in the future will surely promote the development of this field.

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“…When proteins fail to undergo proper protein folding and maturation in the mitochondria, the resulting stress on the organelle leads to the activation of a nuclear transcriptional program termed the mitochondrial unfolded protein response (mtUPR) that aims to increase the transcription of mitochondrial chaperones and proteases to counteract mitochondrial dysfunction 191 . The mtUPR plays an important regulatory role in stem cell proliferation, cellular differentiation, aging, 192 oocyte and embryo development, and oocyte mitochondrial function and dynamics 193 . In the early phase of mtUPR, there is a rapid remodeling of CL, resulting in a changed lipid microenvironment that helps to stabilize protein import machinery upon mtUPR induction 191 …”

Section: Cardiolipin Functions Can Be Linked To Mitochondria and Deve...mentioning

confidence: 99%

The critical role of cardiolipin in metazoan differentiation, development, and maturation

Olivar-Villanueva

Ren

Schlame

et al. 2023

Developmental Dynamics

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Cardiolipins are phospholipids that are central to proper mitochondrial functioning. Because mitochondria play crucial roles in differentiation, development, and maturation, we would also expect cardiolipin to play major roles in these processes. Indeed, cardiolipin has been implicated in the mechanism of three human diseases that affect young infants, implying developmental abnormalities. In this review, we will: (1) Review the biology of cardiolipin; (2) Outline the evidence for essential roles of cardiolipin during organismal development, including embryogenesis and cell maturation in vertebrate organisms; (3) Place the role(s) of cardiolipin during embryogenesis within the larger context of the roles of mitochondria in development; and (4) Suggest avenues for future research.

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Mitochondrial Unfolded Protein Response and Its Roles in Stem Cells

Cited by 15 publications

References 121 publications

A Novel Age-Related Circular RNA Circ-ATXN2 Inhibits Proliferation, Promotes Cell Death and Adipogenesis in Rat Adipose Tissue-Derived Stromal Cells

A Novel Age-Related Circular RNA Circ-ATXN2 Inhibits Proliferation, Promotes Cell Death and Adipogenesis in Rat Adipose Tissue-Derived Stromal Cells

Knowledge mapping of research on the mitochondrial unfolded protein response: a bibliometric and visual analysis

The critical role of cardiolipin in metazoan differentiation, development, and maturation

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